Jeong Yu-Jin, Choi Yean-Jung, Choi Jung-Suk, Kwon Hyang-Mi, Kang Sang-Wook, Bae Ji-Young, Lee Sang-Soo, Kang Jung-Sook, Han Seoung Jun, Kang Young-Hee
Department of Food and Nutrition and Institute of Korea Nutrition Research, Hallym University, Chuncheon, South Korea.
Br J Nutr. 2007 Mar;97(3):447-57. doi: 10.1017/S0007114507657894.
Oxidative modification of LDL is causally involved in the development of atherosclerosis and occurs in vivo in the blood as well as within the vascular wall. The present study attempted to explore whether polyphenolic flavonoids influence monocyte-endothelium interaction and lectin-like oxidised LDL receptor 1 (LOX-1) expression involved in the early development of atherosclerosis. The flavones luteolin and apigenin inhibited THP-1 cell adhesion onto oxidised LDL-activated human umbilical vein endothelial cells (HUVEC), while the flavanols of (-)epigallocatechin gallate and (+)catechin, the flavonols of quercetin and rutin, and the flavanones of naringin, naringenin, hesperidin and hesperetin did not have such effects. Consistently, Western blot analysis revealed that the flavones at 25 microM dramatically and significantly abolished HUVEC expression of vascular cell adhesion molecule-1 and E-selectin evidently enhanced by oxidised LDL; these inhibitory effects were exerted by drastically down regulating mRNA levels of these cell adhesion molecules. In addition, quercetin and luteolin significantly attenuated expression of LOX-1 protein up regulated in oxidised LDL-activated HUVEC with a fall in transcriptional mRNA levels of LOX-1. In addition, quercetin and luteolin clearly blunted oxidised LDL uptake by HUVEC treated with oxidised LDL. The results demonstrate that the flavones luteolin and apigenin as well as quercetin were effective in the different initial steps of atherosclerosis process by inhibiting oxidised LDL-induced endothelial monocyte adhesion and/or oxidised LDL uptake. Therefore, certain flavonoids qualify as anti-atherogenic agents in LDL systems, which may have implications for strategies attenuating endothelial dysfunction-related atherosclerosis.
低密度脂蛋白（LDL）的氧化修饰与动脉粥样硬化的发展有因果关系，且在体内血液以及血管壁中都会发生。本研究试图探讨多酚类黄酮是否会影响单核细胞与内皮细胞的相互作用以及参与动脉粥样硬化早期发展的凝集素样氧化型LDL受体1（LOX-1）的表达。黄酮类化合物木犀草素和芹菜素可抑制THP-1细胞黏附于氧化型LDL激活的人脐静脉内皮细胞（HUVEC），而表没食子儿茶素没食子酸酯和儿茶素的黄烷醇、槲皮素和芦丁的黄酮醇以及柚皮苷、柚皮素、橙皮苷和橙皮素的黄烷酮则没有这种作用。同样，蛋白质印迹分析显示，25微摩尔的黄酮类化合物能显著消除氧化型LDL明显增强的HUVEC血管细胞黏附分子-1和E-选择素的表达；这些抑制作用是通过大幅下调这些细胞黏附分子的mRNA水平来实现的。此外，槲皮素和木犀草素显著减弱了氧化型LDL激活的HUVEC中上调的LOX-1蛋白的表达，同时LOX-1的转录mRNA水平也下降。此外，槲皮素和木犀草素明显减弱了用氧化型LDL处理的HUVEC对氧化型LDL的摄取。结果表明，黄酮类化合物木犀草素、芹菜素以及槲皮素通过抑制氧化型LDL诱导的内皮单核细胞黏附和/或氧化型LDL摄取，在动脉粥样硬化过程的不同初始阶段均有效果。因此，某些黄酮类化合物可作为LDL系统中的抗动脉粥样硬化剂，这可能对减轻与内皮功能障碍相关的动脉粥样硬化的策略具有重要意义。
